Indirect blockade of vascular endothelial growth factor: the potential for eye disease therapy

The process of neovascularization is stimulated by proangiogenic growth factors, particularly vascular endothelial growth factor (VEGF), and the use of intravitreally injected anti-VEGF agents is currently the gold standard of care in the treatment of neovascular retinal pathologies. However, caution is needed as anti-VEGF agents display a variety of limitations and adverse side effects. In addition, there is evidence that VEGF is a neuroprotective factor supporting retinal neurons independently of its actions on vessels, thus direct VEGF blockade may interfere with neuronal survival. Therefore, additional therapies are needed to reduce these potential adverse effects of VEGF blockade. A number of new therapeutic approaches are being tested for their ability to indirectly target the VEGF system reducing retinal VEGF levels or the efficiency of VEGF signaling. Here, we briefly report some experimental observations on substances that may indirectly inhibit the deleterious effects of VEGF in eye disease.